A 14 amino acid cystin bridge containing neuropeptide was discovered in 1973 and designated as growth hormone-inhibiting hormone, in other words, somatostatin. Its discovery led to the synthesis of three analogs which were licensed for the treatment of acromegaly: octreotide, lanreotide and pasireotide. Somatostatin analogs are currently approved only as either subcutaneous or intramuscular long-acting injections. We examine the challenges that must be overcome to create oral formulations of somatostatin analogs and examine selected clinical trial data. While octreotide has low intestinal permeability, similar to almost all other peptides, it has an advantage of being more stable against intestinal peptidases. The development of new oral formulation strategies may eventually allow for the successful oral administration of potent somatostatin analogs with high therapeutic indices.
Keywords: acromegaly; intestinal permeability; octreotide; oral peptide delivery; somatostatin.